Haemophilus influenzae (formerly called Pfeiffer's bacillus or
Bacillus influenzae) is a Gram-negative, coccobacillary, facultatively
anaerobic pathogenic bacterium belonging to the Pasteurellaceae
family. H. influenzae was first described in 1892 by Richard Pfeiffer
during an influenza pandemic.
The bacterium was mistakenly considered to be the cause of influenza
until 1933 when the viral cause of influenza became apparent, and is
still colloquially known as 'bacterial influenza'. H. influenzae is
responsible for a wide range of localized and invasive infections.
This species was the first free-living organism to have its entire
3.2 Latex particle agglutination
3.3 Molecular methods
4 Interaction with Streptococcus pneumoniae
5 Signs and symptoms
7 Serious complications
10 Likely protective role of transformation
11 See also
13 External links
In 1930, two major categories of H. influenzae were defined: the
unencapsulated strains and the encapsulated strains. Encapsulated
strains were classified on the basis of their distinct capsular
antigens. There are six generally recognized types of encapsulated H.
influenzae: a, b, c, d, e, and f. Genetic diversity among
unencapsulated strains is greater than within the encapsulated group.
Unencapsulated strains are termed nontypable (NTHi) because they lack
capsular serotypes; however, they can be classified by multilocus
sequence typing. The pathogenesis of H. influenzae infections is not
completely understood, although the presence of the capsule in
encapsulated type b (Hib), a serotype causing conditions such as
epiglottitis, is known to be a major factor in virulence. Their
capsule allows them to resist phagocytosis and complement-mediated
lysis in the nonimmune host. The unencapsulated strains are almost
always less invasive; they can, however, produce an inflammatory
response in humans, which can lead to many symptoms. Vaccination with
Hib conjugate vaccine is effective in preventing Hib infection, but
does not prevent infection with NTHi strains.
Haemophilus influenzae infection
Classification and external resources
[edit on Wikidata]
Most strains of H. influenzae are opportunistic pathogens; that is,
they usually live in their host without causing disease, but cause
problems only when other factors (such as a viral infection, reduced
immune function or chronically inflamed tissues, e.g. from allergies)
create an opportunity. They infect the host by sticking to the host
cell using trimeric autotransporter adhesins.
Naturally acquired disease caused by H. influenzae seems to occur in
humans only. In infants and young children, H. influenzae type b (Hib)
causes bacteremia, pneumonia, epiglottitis and acute bacterial
meningitis. On occasion, it causes cellulitis, osteomyelitis, and
infectious arthritis. It is one cause of neonatal infection.
Due to routine use of the Hib conjugate vaccine in the U.S. since
1990, the incidence of invasive Hib disease has decreased to
1.3/100,000 in children. However, Hib remains a major cause of lower
respiratory tract infections in infants and children in developing
countries where the vaccine is not widely used. Unencapsulated H.
influenzae strains are unaffected by the
Hib vaccine and cause ear
infections (otitis media), eye infections (conjunctivitis), and
sinusitis in children, and are associated with pneumonia.
H. influenzae, in a
Gram stain of a sputum sample, appear as
Haemophilus influenzae requires X and V factors for growth. In this
culture haemophilus has only grown around the paper disc that has been
impregnated with X and V factors. There is no bacterial growth around
the discs that only contain either X or V factor.
Chest X-ray of a case of
Haemophilus influenzae, presumably as a
secondary infection from influenza.
Chest X-ray in a case of
COPD exacerbation where a nasopharyngeal swab
Haemophilus influenzae. There are opacities (on the patient's
right side), which however can be seen in other types of pneumonia as
Clinical features may include initial symptoms of an upper respiratory
tract infection mimicking a viral infection, usually associated with
fevers, often low-grade. This may progress to the lower respiratory
tract in a few days, with features often resembling those of a wheezy
bronchitis. Sputum may be difficult to expectorate and is often grey
or creamy in color. The cough may persist for weeks without
appropriate treatment. Many cases are diagnosed after presenting chest
infections do not respond to penicillins or first-generation
cephalosporins. A chest X-ray can identify alveolar consolidation.
Clinical diagnosis of H. influenzae is typically performed by
bacterial culture or latex particle agglutinations. Diagnosis is
considered confirmed when the organism is isolated from a sterile body
site. In this respect, H. influenzae cultured from the nasopharyngeal
cavity or sputum would not indicate H. influenzae disease, because
these sites are colonized in disease-free individuals. However, H.
influenzae isolated from cerebrospinal fluid or blood would indicate
H. influenzae infection.
Bacterial culture of H. influenzae is performed on agar plates, the
preferable one being chocolate agar, with added X (hemin) and V
(nicotinamide adenine dinucleotide) factors at 37 °C in a
CO2-enriched incubator. Blood agar growth is only achieved as a
satellite phenomenon around other bacteria. Colonies of H. influenzae
appear as convex, smooth, pale, grey or transparent colonies.
Gram-stained and microscopic observation of a specimen of H.
influenzae will show
Gram-negative coccobacillus. The cultured
organism can be further characterized using catalase and oxidase
tests, both of which should be positive. Further serological testing
is necessary to distinguish the capsular polysaccharide and
differentiate between H. influenzae b and nonencapsulated species.
Although highly specific, bacterial culture of H. influenzae lacks in
sensitivity. Use of antibiotics prior to sample collection greatly
reduces the isolation rate by killing the bacteria before
identification is possible. Beyond this, H. influenzae is a
finicky bacterium to culture, and any modification of culture
procedures can greatly reduce isolation rates. Poor quality of
laboratories in developing countries has resulted in poor isolation
rates of H. influenzae.
H. influenzae will grow in the hemolytic zone of Staphylococcus aureus
on blood agar plates; the hemolysis of cells by S. aureus releases
factor V which is needed for its growth. H. influenzae will not grow
outside the hemolytic zone of S. aureus due to the lack of nutrients
such as factor V in these areas. Fildes agar is best for isolation. In
Levinthal medium, capsulated strains show distinctive iridescence.
Latex particle agglutination
The latex particle agglutination test (LAT) is a more sensitive method
to detect H. influenzae than is culture. Because the method relies
on antigen rather than viable bacteria, the results are not disrupted
by prior antibiotic use. It also has the added benefit of being much
quicker than culture methods. However, antibiotic sensitivity testing
is not possible with LAT alone, so a parallel culture is necessary.
Polymerase chain reaction
Polymerase chain reaction (PCR) assays have been proven to be more
sensitive than either LAT or culture tests, and highly specific.
However, PCR assays have not yet become routine in clinical settings.
Countercurrent immunoelectrophoresis has been shown to be an effective
research diagnostic method, but has been largely supplanted by PCR.
Interaction with Streptococcus pneumoniae
Both H. influenzae and S. pneumoniae can be found in the upper
respiratory system of humans. In an in vitro study of competition, S.
pneumoniae always overpowered H. influenzae by attacking it with
hydrogen peroxide and stripping off the surface molecules H.
influenzae needs for survival.
When both bacteria are placed together into a nasal cavity, within 2
weeks, only H. influenzae survives. When either is placed separately
into a nasal cavity, each one survives. Upon examining the upper
respiratory tissue from mice exposed to both bacteria species, an
extraordinarily large number of neutrophils (immune cells) was found.
In mice exposed to only one of the species, the neutrophils were not
Lab tests showed neutrophils exposed to dead H. influenzae were more
aggressive in attacking S. pneumoniae than unexposed neutrophils.
Exposure to dead H. influenzae had no effect on live H. influenzae.
Two scenarios may be responsible for this response:
When H. influenzae is attacked by S. pneumoniae, it signals the immune
system to attack the S. pneumoniae
The combination of the two species triggers an immune system response
that is not set off by either species individually.
It is unclear why H. influenzae is not affected by the immune
Signs and symptoms
Pneumonia occurs when the lungs become infected, causing inflammation
(swelling). Symptoms of pneumonia usually include:
Fever (but older people may have lower than normal body temperature)
Shortness of breath
Chest pain that comes and goes with breathing
Nails may turn blue from lack of oxygen
Haemophilus influenzae produces beta-lactamases, and it is also able
to modify its penicillin-binding proteins, so it has gained resistance
to the penicillin family of antibiotics. In severe cases, cefotaxime
and ceftriaxone delivered directly into the bloodstream are the
elected antibiotics, and, for the less severe cases, an association of
ampicillin and sulbactam, cephalosporins of the second and third
generation, or fluoroquinolones are preferred.
Haemophilus influenzae have been
Macrolide antibiotics (e.g., clarithromycin) may be used in patients
with a history of allergy to beta-lactam antibiotics.
Macrolide resistance has also been observed.
The serious complications of HiB are brain damage, hearing loss, and
Effective vaccines for
Haemophilus influenzae Type B have been
available since the early 1990s, and is recommended for children under
age 5 and asplenic patients. The
World Health Organization
World Health Organization recommends
a pentavalent vaccine, combining vaccines against diphtheria, tetanus,
pertussis, hepatitis B and Hib. There is not yet sufficient evidence
on how effective this pentavalent vaccine is in relation to the
Hib vaccines cost about seven times the total cost of vaccines against
measles, polio, tuberculosis, diphtheria, tetanus, and pertussis.
Consequently, whereas 92% of the populations of developed countries
was vaccinated against Hib as of 2003, vaccination coverage was 42%
for developing countries, and only 8% for least-developed
The Hib vaccines do not provide cross-protection to any other
Haemophilus influenzae serotypes like Hia, Hic, Hid, Hie or Hif.
H. influenzae was the first free-living organism to have its entire
genome sequenced. Completed by Craig Venter and his team at The
Institute for Genomic Research - one of the institutes now part of the
J. Craig Venter Institute.
Haemophilus was chosen because one of the
project leaders, Nobel laureate Hamilton Smith, had been working on it
for decades and was able to provide high-quality DNA libraries. The
genome consists of 1,830,140 base pairs of DNA in a single circular
chromosome that contains 1740 protein-coding genes, 2 transfer RNA
genes, and 18 other RNA genes. The sequencing method used was
whole-genome shotgun, which was completed and published in Science in
Likely protective role of transformation
Unencapsulated H. influenzae is often observed in the airways of
patients with chronic obstructive pulmonary disease (COPD).
Neutrophils are also observed in large numbers in sputum from patients
with COPD. The neutrophils phagocytize H. influenzae, thereby
activating an oxidative respiratory burst. However instead of
killing the bacteria the neutrophils are themselves killed (though
such an oxidative burst likely causes DNA damage in the H. influenzae
cells). The lack of killing of the H. influenzae appears to explain
the persistence of infection in COPD.
H. influenzae mutants defective in the rec1 gene (a homolog of recA)
are very sensitive to killing by the oxidizing agent hydrogen
peroxide. This finding suggests that rec1 expression is important
for H. influenzae survival under conditions of oxidative stress. Since
it is a homolog of recA, rec1 likely plays a key role in
recombinational repair of DNA damage. Thus H. influenzae may protect
its genome against the reactive oxygen species produced by the
host’s phagocytic cells through recombinational repair of oxidative
DNA damages. Recombinational repair of a damaged site of a
chromosome requires, in addition to rec1, a second homologous
undamaged DNA molecule. Individual H. influenzae cells are capable of
taking up homologous DNA from other cells by the process of
transformation. Transformation in H. influenzae involves at least 15
gene products, and is likely an adaptation for repairing DNA
damages in the resident chromosome (as suggested in Transformation
(genetics)#Transformation, as an adaptation for DNA repair).
Vaccines that target unencapsulated H. influenzae serotypes are in
Wikimedia Commons has media related to
Haemophilus influenzae cellulitis
Trimeric Autotransporter Adhesins (TAA)
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Haemophilus influenzae". NCBI Taxonomy Browser. 727.
Type strain of
Haemophilus influenzae at
BacDive - the Bacterial
Bacterial disease: Proteobacterial G−
primarily A00–A79, 001–041, 080–109
Epidemic typhus, Brill–Zinsser disease, Flying squirrel typhus
Rocky Mountain spotted fever
Japanese spotted fever
North Asian tick typhus
Queensland tick typhus
Flinders Island spotted fever
African tick bite fever
American tick bite fever
Rickettsia aeschlimannii infection
Flea-borne spotted fever
Ehrlichiosis: Anaplasma phagocytophilum
Human granulocytic anaplasmosis, Anaplasmosis
Human monocytotropic ehrlichiosis
Ehrlichiosis ewingii infection
Bartonellosis: Bartonella henselae
Either B. henselae or B. quintana
Carrion's disease, Verruga peruana
Meningococcal disease, Waterhouse–Friderichsen syndrome,
Eikenella corrodens/Kingella kingae
Burkholderia cepacia complex
Bordetella pertussis/Bordetella parapertussis
Rhinoscleroma, Klebsiella pneumonia
Escherichia coli: Enterotoxigenic
Enterobacter aerogenes/Enterobacter cloacae
Citrobacter koseri/Citrobacter freundii
Typhoid fever, Paratyphoid fever, Salmonellosis
Shigellosis, Bacillary dysentery
Proteus mirabilis/Proteus vulgaris
Far East scarlet-like fever
Brazilian purpuric fever
Legionella pneumophila/Legionella longbeachae
Aeromonas hydrophila/Aeromonas veronii
Campylobacteriosis, Guillain–Barré syndrome
Peptic ulcer, MALT lymphoma, Gastric cancer